A structural, genetic and clinical comparison of CAR-T cells and CAR-NK cells: companions or competitors? - Review

Sep 21, 2026

Review examining the development of engineered chimeric antigen receptor (CAR) immune-cell therapies after major advances in CAR-T for hematological cancers. Compares CAR-T with CAR-NK cells by focusing on structural, genetic, and clinical characteristics, and highlights their functional differences. Discusses the “off-the-shelf” potential of adoptive CAR-NK therapy alongside key limitations, especially reduced in-body persistence that can limit sustained anti-tumor efficacy, and positions the field toward precision, ready-to-use treatments.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages21

Reading Time53 min

AccessFree to download

1 Introduction

2 CAR structure

2.1 Different generations of CAR-T cells and CAR-NK cells

TYPE Review PUBLISHED 04 October 2024 DOI 10.3389/fimmu.2024.1459818 OPEN ACCESS EDITED BY Scott McComb, National Research Council Canada (NRC), Canada REVIEWED BY Sam Kung, University of Manitoba, Canada Katarina Mirjacic Martinovic, Institute of Oncology and Radiology of Serbia, Serbia *CORRESPONDENCE Salima Hacein-Bey-Abina [salima.hacein-bey-abina@u-paris.fr](salima.hacein-bey-abina@u-paris.fr); [salima.hacein-bey@aphp.fr](salima.hacein-bey@aphp.fr) †These authors have contributed equally to this work RECEIVED 04 July 2024 ACCEPTED 16 September 2024 PUBLISHED 04 October 2024 CITATION Andrea AE, Chiron A, Sarrabayrouse G, Bessoles S and Hacein-Bey-Abina S (2024) A structural, genetic and clinical comparison of CAR-T cells and CAR-NK cells: companions or competitors?. Front. Immunol. 15:1459818 . doi: 10.3389/fimmu.2024.1459818 COPYRIGHT © 2024 Andrea, Chiron, Sarrabayrouse, Bessoles and Hacein-Bey-Abina. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. A structural, genetic and clinical comparison of CAR-T cells and CAR-NK cells: companions or competitors? Alain E. Andrea 1†, Andrada Chiron 2,3†, Guillaume Sarrabayrouse 2, St´ephanie Bessoles 2† and Salima Hacein-Bey-Abina 2,3*† 1 Department of Biology, Faculty of Arts and Sciences, Saint George University of Beirut, Beirut, Lebanon, 2 Universite´ Paris Cite´ , Centre National de la Recherche Scientiﬁque, Institut National de la Sante´ et de la Recherche Me´ dicale, Unite´ des Technologies Chimiques et Biologiques pour la Sante´ (UTCBS), Paris, France, 3Clinical Immunology Laboratory, Groupe Hospitalier Universitaire Paris Saclay, Hˆopital Bicˆetre, Assistance Publique-Hˆopitaux de Paris, Le-Kremlin-Bicˆetre, France In recent years, following the groundbreaking achievements of chimeric antigen receptor (CAR) T cell therapy in hematological cancers, and advancements in cell engineering technologies, the exploration of other immune cells has garnered signiﬁcant attention. CAR-Therapy extended beyond T cells to include CAR natural killer (NK) cells and CAR-macrophages, which are ﬁrmly established in the clinical trial landscape. Less conventional immune cells are also making their way into the scene, such as CAR mucosal-associated invariant T (MAIT) cells. This progress is advancing precision medicine and facilitating the development of ready-to-use biological treatments. However, in view of the unique features of natural killer cells, adoptive NK cell immunotherapy has emerged as a universal, allogenic, “off-the shelf” therapeutic strategy. CAR-NK cytotoxic cells present targeted tumor speciﬁcity but seem to be devoid of the side effects associated with CAR-T cells. CAR-NK cells appear to be potentially promising candidates for cancer immunotherapy. However, their application is hindered by signiﬁcant challenges, particularly the limited persistence of CAR-NK cells in the body, which poses a hurdle to their sustained effectiveness in treating cancer. Based upon the foregoing, this review discusses the current status and applications of both CAR-T cells and CAR-NK cells in hematological cancers, and provides a comparative analysis of the structure, genetics, and clinical outcomes between these two types of genetically modiﬁed immune cells. KEYWORDS CAR-T cells, CAR-NK cells, Cytokines, Hematological malignancies, Off-the-shelf Immunotherapies Frontiers in Immunology 01 [frontiersin.org](frontiersin.org) 1 Introduction Cellular immunotherapy [also known as adoptive cell therapy (ACT)] has produced signiﬁcant progr

FAQs

What therapies are compared in this review?

The review compares CAR-T cells and CAR-NK cells for hematological cancers, analyzing how their structure, genetics, and clinical outcomes relate to performance.

Why is CAR-NK therapy considered an “off-the-shelf” strategy?

Because natural killer–based adoptive immunotherapy can be designed for universal, allogeneic use, enabling ready-to-use biological treatments rather than relying solely on patient-derived material.

What major challenge limits CAR-NK effectiveness?

A key limitation is the limited persistence of CAR-NK cells in the body, which can hinder sustained anti-cancer activity.

Sep 21, 2026

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